The interplay of transcription factors and cis-regulatory elements (CREs) orchestrates the dynamic and diverse genetic programs that assemble the human central nervous system (CNS) during development and maintain its function throughout life. Genetic variation within CREs plays a central role in phenotypic variation in complex traits including the risk of developing disease. We took advantage of the retina, a well-characterized region of the CNS known to be affected by pathogenic variants in CREs, to establish a roadmap for characterizing regulatory variation in the human CNS. This comprehensive analysis of tissue-specific regulatory elements, transcription factor binding, and gene expression programs in three regions of the human visual system (retina, macula, and retinal pigment epithelium/choroid) reveals features of regulatory element evolution that shape tissue-specific gene expression programs and defines regulatory elements with the potential to contribute to Mendelian and complex disorders of human vision.

A Fokker-Planck treatment of the current induced by a beam of fast ions circulating in a toroidal plasma is developed. The electron Fokker-Planck equation is first reduced to an integro-differential equation which is then solved analytically in the limiting cases of: (a) a large plasma Z and (b) a large ratio of the electron thermal velocity ve to the fast ion velocity vb. In addition, a numerical solution was obtained for the complete range of values of ve/vb and for several values of Z. It is found that the resulting net plasma current has a very different functional dependence upon electron temperature than that given by the conventional theoretical treatment in which the electrons are assumed to be Maxwellian. In particular, for ve > vb and Z = 1, which is the limit appropriate to many present tokamak experiments, the net current is found to be in the opposite direction to the fast-ion current. The theory is compared with recent measurements of this current which were made by using the Culham Levitron, and agreement is found between theory and experiment.

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Leber congenital amaurosis (LCA) is a severe disease that leads to complete blindness in children, typically before the first year of life. Due to the clinical and genetic heterogeneity among LCA and other retinal diseases, providing patients with a molecular diagnosis is essential to assigning an accurate clinical diagnosis. Using our gene panel that targets 300 genes that are known to cause retinal disease, including 24 genes reported to cause LCA, we sequenced 43 unrelated probands with Brazilian ancestry. We identified 42 unique variants and were able to assign a molecular diagnosis to 30/43 (70%) Brazilian patients. Among these, 30 patients were initially diagnosed with LCA or a form of early-onset retinal dystrophy, 17 patients harbored mutations in LCA-associated genes, while 13 patients had mutations in genes that were reported to cause other diseases involving the retina.